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Article in Chinese | WPRIM | ID: wpr-928389


OBJECTIVE@#To analyze the clinical features and genetic basis for a Chinese pedigree affected with hereditary dyschromatosis symmetrica hereditaria (DSH).@*METHODS@#Peripheral blood samples of the proband and his mother were collected and subjected to PCR and Sanger sequencing.@*RESULTS@#The patient has conformed to the typical pattern of DSH and manifested with hyperpigmentation, hypo- and hyperpigmentation spots on the back of hands, feet and face. Sanger sequencing confirmed that the proband and his mother have both harbored heterozygous splicing variant c.2762+1G>T in exon 9 of the ADAR gene, which was unreported previously. The same variant was not detected among 100 healthy controls. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4).@*CONCLUSION@#The c.2762+1G>T variant of the ADAR gene probably underlay the DSH in this pedigree. Above finding has enriched the spectrum of ADAR gene mutations.

Adenosine Deaminase/genetics , China , Humans , Mutation , Pedigree , Pigmentation Disorders/congenital , RNA-Binding Proteins/genetics
Article in Chinese | WPRIM | ID: wpr-928363


OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH).@*METHODS@#PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree.@*RESULTS@#The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual.@*CONCLUSION@#The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.

Adenosine Deaminase/genetics , China , Female , Humans , Mutation , Pedigree , Pigmentation Disorders/congenital , RNA-Binding Proteins/genetics
Article in Chinese | WPRIM | ID: wpr-879473


OBJECTIVE@#To detect variants of ADAR1 gene in two Chinese pedigrees affected with dyschromatosis symmetrica hereditaria (DSH).@*METHODS@#Clinical data and peripheral blood samples of the pedigrees were collected. All exons of the ADAR1 gene were amplified by PCR and subjected to Sanger sequencing. Suspected pathogenic variants were validated among other members of the pedigrees and 100 unrelated healthy controls.@*RESULTS@#For pedigree 1, Sanger sequencing has identified a heterozygous missense variant c.3002G>C (p.Asp968His) in exon 11 of the ADAR1 gene in the proband and his father. For pedigree 2, a novel nonsense variant c.3145C>T (p.Gln1049Ter) was identified in exon 12 of the ADAR1 gene in the proband and his son, which were previously unreported and absent among the healthy controls.@*CONCLUSION@#The c.3002G>C (p.Asp968His) and c.3145C>T (p.Gln1049Ter)variants of the ADAR1 gene probably underlay the DSH in the two pedigrees.

Adenosine Deaminase/genetics , Humans , Mutation , Pedigree , Pigmentation Disorders/genetics , RNA-Binding Proteins/genetics
Biol. Res ; 51: 36, 2018. graf
Article in English | LILACS | ID: biblio-983940


BACKGROUND: Whole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA ( ADAR ) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed. RESULTS: We characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3'UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1. Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3'UTRs. Interestingly, editing was particularly increased in the 3'UTRs of ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1). CONCLUSIONS: Altogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer.

Humans , Female , Breast Neoplasms/genetics , Adenosine Deaminase/genetics , RNA-Binding Proteins/genetics , RNA Editing/genetics , Untranslated Regions/genetics , RNA Stability/genetics , Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Adenosine Deaminase/metabolism , RNA-Binding Proteins/metabolism , Gene Expression Profiling , RNA Stability/physiology , Cell Line, Tumor
Pulmäo RJ ; 25(1): 11-16, 2016.
Article in Portuguese | LILACS | ID: biblio-848939


Depois de introduzir os conceitos básicos da enzima adenosina desaminase (ADA), uma breve discussão sobre a estrutura, o mecanismo enzimático, terapia genética e potencial utilização terapêutica de inibidores de ADA são apresentados. O estudo da ADA é muito mais complexo do que simplesmente seu papel como biomarcador diagnóstico para tuberculose pleural que veio revolucionar o setor de diagnóstico na medicina clínica nos últimos anos. O aumento de sua atividade no líquido pleural, e em outros líquidos orgânicos, impede que o paciente na maioria dos casos com síndrome do derrame pleural por tuberculose seja submetido a procedimentos cirúrgicos invasivos com possíveis complicações potencialmente fatais AU.

After introducing the basic concepts of ADA, a brief discussion on the structure, enzymatic mechanism, gene therapy and potential therapeutic use of ADA inhibitors are presented. The study of the ADA is much more complex than simply its role as a biomarker for pleural tuberculosis that has revolutionized the diagnostic in clinical medicine in recent years. The increase in its activity in the pleural fluid, and other body fluids, prevents the patient in most cases with pleural effusion tuberculosis is subjected to invasive surgical procedures with possible life-threatening complications. AU

Humans , Tuberculosis, Pleural/diagnosis , Adenosine Deaminase/genetics , Adenosine Deaminase/ultrastructure , Adenosine Deaminase Inhibitors/therapeutic use
Clinics ; 66(11): 1929-1933, 2011. ilus, tab
Article in English | LILACS | ID: lil-605874


OBJECTIVE: Adenosine deaminase acts on adenosine and deoxyadenosine metabolism and modulates the immune response. The adenosine deaminase G22A polymorphism (20q.11.33) influences the level of adenosine deaminase enzyme expression, which seems to play a key role in maintaining pregnancy. The adenosine deaminase 2 phenotype has been associated with a protective effect against recurrent spontaneous abortions in European Caucasian women. The aim of this study was to investigate whether the G22A polymorphism of the adenosine deaminase gene is associated with recurrent spontaneous abortions in Brazilian women. METHODS: A total of 311 women were recruited to form two groups: G1, with a history of recurrent spontaneous abortions (N = 129), and G2, without a history of abortions (N = 182). Genomic DNA was extracted from peripheral blood with a commercial kit and PCR-RFLP analysis was used to identify the G22A genetic polymorphism. Fisher's exact test and odds ratio values were used to compare the proportions of adenosine deaminase genotypes and alleles between women with and without a history of recurrent spontaneous abortion (p<0.05). The differences between mean values for categorical data were calculated using unpaired t tests. The Hardy-Weinberg equilibrium was assessed with a chi-square test. RESULTS: Statistically significant differences were identified for the frequencies of adenosine deaminase genotypes and alleles between the G1 and G2 groups when adjusted for maternal age. CONCLUSIONS:The results suggest that the adenosine deaminase *2 allele is associated with a low risk for recurrent spontaneous abortions, but this association is dependent on older age.

Adult , Female , Humans , Pregnancy , Alleles , Abortion, Habitual/genetics , Adenosine Deaminase/genetics , Polymorphism, Genetic/genetics , Age Factors , Abortion, Habitual/epidemiology , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/genetics , Brazil/epidemiology , Case-Control Studies , Chi-Square Distribution , Genotype
Invest. clín ; 51(4): 561-571, dic. 2010. ilus
Article in Spanish | LILACS | ID: lil-630913


La adenosin deaminasa (ADA), es una enzima del metabolismo de las purinas que ha sido objeto de mucho interés debido a que el defecto congénito de esta enzima causa el síndrome de inmunodeficiencia combinada severa. Una de las tres isoformas de la enzima (ecto-ADA) es capaz de unirse a la glicoproteína CD26 y a los receptores de adenosina A1 y A2B. La interacción ADA-CD26 produce una señal coestimuladora en los eventos de activación de las células T y en la secreción de IFN-g, TNF-a e IL-6. Durante dicha activación la actividad de la enzima está regulada de manera positiva por IL-2 e IL-12 y negativamente por IL-4, basado en un mecanismo de translocación. Diversos estudios señalan que los niveles séricos y plasmáticos de ADA se elevan en algunas enfermedades causadas por microorganismos que infectan principalmente a los macrófagos; así como en trastornos hipertensivos, lo cual podría representar un mecanismo compensatorio como consecuencia de la elevación de los niveles de adenosina y la liberación de mediadores hormonales e inflamatorios estimulados por la hipoxia.

Adenosine deaminase (ADA) is an enzyme of purine metabolism which has been the subject of much interest because the congenital defect of this enzyme causes severe combined immunodeficiency syndrome. One of the three isoforms of the enzyme (ecto-ADA) is capable of binding to the glycoprotein CD26 and adenosine receptors A1 and A2B. ADA-CD26 interaction produces a costimulatory signal in the events of T cell activation and secretion of IFN-g, TNF-a and IL-6. During this activation, the enzyme activity is regulated positively by IL-2 and IL-12 and negatively by IL-4, based on the mechanism of translocation. Diverse studies suggest that seric and plasmatic levels of ADA rise in some diseases caused by microorganisms infecting mainly the macrophages and in hypertensive disorders, which may represent a compensatory mechanism resulting from increased adenosine levels and the release of hormones and inflammatory mediators estimulated by hipoxia.

Female , Humans , Pregnancy , Adenosine Deaminase/physiology , Immunity, Cellular , Adenosine Deaminase/blood , Adenosine Deaminase/deficiency , Adenosine Deaminase/genetics , Adenosine Deaminase/immunology , Adenosine/physiology , Agammaglobulinemia/genetics , Agammaglobulinemia/immunology , Cell Hypoxia , Communicable Diseases/enzymology , Communicable Diseases/immunology , Dendritic Cells/enzymology , Dendritic Cells/immunology , /physiology , Enzyme Induction , Hepatitis, Viral, Human/enzymology , Hepatitis, Viral, Human/immunology , Hypertension, Pregnancy-Induced/enzymology , Hypertension, Pregnancy-Induced/physiopathology , Immunological Synapses , Inflammation Mediators/metabolism , Interferon-gamma , Interleukins , Isoenzymes/physiology , Lymphocyte Activation , Receptors, Purinergic P1/physiology , Severe Combined Immunodeficiency/genetics , Severe Combined Immunodeficiency/immunology , T-Lymphocytes/immunology , T-Lymphocytes , Tumor Necrosis Factor-alpha
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 32(3): 275-278, Sept. 2010. tab
Article in English | LILACS | ID: lil-560771


OBJECTIVE: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A) (ADA1*2) exhibits 20-30 percent lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G→A (ADA1*2) in schizophrenic patients and healthy controls. METHOD: The genotypes of the ADA 22G→A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. RESULTS: A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6 percent) relative to controls (13/111 - 11.7 percent, p = 0.032, OR = 2.6). CONCLUSION: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients.

OBJETIVO: A adenosina pode ter um papel importante na fisiopatologia da esquizofrenia, uma vez que modula a liberação de vários neurotransmissores, tais como glutamato, dopamina, serotonina e acetilcolina, diminui a atividade neuronal por hiperpolarização pós-sináptica e inibe a atividade dopaminérgica. A adenosina desaminase participa do metabolismo das purinas pela conversão de adenosina em inosina. O mais frequente polimorfismo funcional da adenosina desaminase (22G →A) (ADA1*2) exibe uma diminuição de 20-30 por cento da atividade funcional em indivíduos com genótipo G/A quando comparados com indivíduos com o genótipo G/G. O objetivo deste estudo foi avaliar o polimorfismo 22G→A (ADA1*2) em pacientes esquizofrênicos e em controles saudáveis. MÉTODO: Os genótipos da ADA 22G →A foram identificados através de uma estratégia de PCR alelo-específica em 152 pacientes esquizofrênicos e 111 controles saudáveis. RESULTADOS: Foi observada uma diminuição significativa na frequência do genótipo G/A em pacientes esquizofrênicos (7 - 4,6 por cento) em relação ao grupo controle (13 - 11,7 por cento, p = 0,032, OR = 2,6). CONCLUSÃO: Estes resultados sugerem que o genótipo G/A associado com baixa atividade de adenosina desaminase, e potencialmente com níveis aumentados de adenosina, é menos frequente entre pacientes esquizofrênicos.

Adult , Female , Humans , Male , Adenosine Deaminase/genetics , Gene Frequency , Polymorphism, Genetic , Schizophrenia/enzymology , Adenosine Deaminase/physiology , Alleles , Case-Control Studies , Genotype , Schizophrenia/physiopathology
Rev. bras. genét ; 11(3): 643-52, sept. 1988. ilus, tab
Article in English | LILACS | ID: lil-65438


Dados sobre os tipos de adenosina deaminase säo reportados em 1067 espécimes de Alouatta belzebul belzebul procedentes da regiäo do rio Tocantins, na Amazônia Brasileira. Oito fenótipos eletroforéticos foram observados, codificados provavelmente por 4 alelos. O grau de polimorfismo observado pode ser classificado como moderno. Dados da literatura indicam que cerca de 40% das espécies de macacos do Velho Mundo e 2 espécies do Novo Mundo säo monomórficas para este locus, e nas espécies ocorre variaçäo, 2-3 alelos säo observados. Em Alouatta belzebul o cromossomo Y está translocado para um autossomo. O locus ADA näo está em desequilíbrio de ligaçäo com os genes determinantes do sexo masculino, e portanto, ou este locus näo está localizado no autossomo indicado, ou está distante da regiäo na qual estes genes foram relocados

Animals , Adenosine Deaminase/genetics , Alouatta/genetics , Polymorphism, Genetic , Alleles , Y Chromosome